Our data reveal an association between toxic concentrations for a number of β-lactam agents and neurotoxic/nephrotoxic effects. We have defined threshold concentrations above which these toxicities become more likely. Clinicians should balance concerns for therapeutic efficacy with potential toxicity when considering aggressive therapy.

To determine whether target concentration non-attainment can be anticipated in critically ill patients prior to initiating empiric β-lactam antibiotic therapy based on readily available clinical factors. Retrospective review of consecutive patients treated with piperacillin or meropenem and who underwent therapeutic drug monitoring (TDM) at St Vincent's Hospital (Sydney, Australia) between January 2013 and December 2015 was performed. Predefined subgroups were patients who received continuous renal replacement therapy (CRRT) and those who did not (non-CRRT). Potential risk factors were evaluated by correlation with β-lactam antibiotic trough concentrations (C) lower than or equal to targeted minimum inhibitory concentration (MIC). Only the first drug concentration after initiation of the antibiotic treatment was included to reflect empirical dose selection. A total of n = 249 patients (piperacillin, n = 169; meropenem, n = 80) were investigated. For non-CRRT patients (n = 210), multivariate analysis demonstrated the following: male gender (p = 0.006); younger age (p = 0.015); prescribed daily antibiotic dose less than 1.5 times the product information recommendations (p = 0.004); lack of positive microbiology (p = 0.006); lower overall illness severity (p = 0.005); and estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m (p < 0.001), to be associated with C ≤ MIC. No predictor variable was found to be significantly associated with C ≤ MIC for the CRRT cohort. Evaluating the risk of target concentration non-attainment using simple clinical factors is possible at the bedside for non-CRRT patients prior to empiric antibiotic initiation. Clinicians should be wary of selecting doses based on the product information especially when treating younger male patients with apparently 'normal' renal function.

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The purpose of the study was to assess the status of emerging therapeutic drug monitoring (TDM) of anti-infective agents in Australian hospitals.Methods: A nationwide cross-sectional survey of all Australian hospitals operating in the public and private health sector was conducted between August and September 2019. The survey consisted of questions regarding institutional TDM practice for anti-infective agents and clinical vignettes specific to β-lactam antibiotics.The authors confirm that the Principal Investigator for this paper is Indy Sandaradura and that he had direct responsibility for participant recruitment and the conduct of the study.

Background: Rotator cuff tears are a common shoulder pathology with an increasing incidence. The optimum post-operative rehab protocol remains unclear and can consist of either conservative rehabilitation or more aggressive early range-of-motion. Multiple studies have assessed these treatment protocols. This meta-analysis aims to compare post-operative clinical outcomes following either conservative or aggressive rehabilitation post rotator cuff repair. Methods: A systematic electronic literature search was undertaken using a number of databases. Eligible studies included randomized control trials published between January 2013 and April 2019 in English with patients having had received rotator cuff repair. Post-operative clinical outcomes considered included shoulder range-of-motion, overall function status (Costant-Murley score) and rates of rotator-cuff re-tear. Studies were evaluated for methodological quality in accordance with the Physiotherapy Evidence Database (PEDro) scale. Summarized pooled statistics were calculated using Review Manager (v5.3) software. Results: A total of six randomized controlled trials were included. Standardized mean difference (SMD) in shoulder flexion, abduction and external rotation was not statistically significant at either 6 or 12 months post rotator cuff repair. Functional assessment suggests a slight benefit in Constant-Murley Score (SMD = 1.77; 95% CI À3.93, 7.47) in aggressive treatment groups with no significant risk increase for cuff re-tear (RR = 1.22; 95% CI 0.60, 2.47). Conclusion: This meta-analysis suggests there is no clear benefit of either rehabilitation protocol when considering range-of-motion, with a possible benefit in functional outcome at the cost of increased re-tear risk post aggressive rehabilitation. Both protocols have been shown to offer safe reproducible short-and long-term outcomes.

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A 32-year-old man presented with a 7-day history of generalised headache, intermittent fever, emesis and diarrhoea. Four days after symptom onset, he developed a vesicular rash on his medial left thigh, without associated pain, paraesthesia or pruritus. He had no significant past medical history, and no HIV risk factors. He was presumed to have enteroviral meningitis and was commenced on supportive therapy. Lumbar puncture was performed and cerebrospinal fluid (CSF) analysis revealed a lymphocytic pleocytosis. While awaiting CSF serology, the formation of a new vesicle was noted at the site of the rash and was swabbed. Results for both the CSF and vesicle swab returned positive for varicella-zoster virus (VZV) confirming concurrent VZV meningitis with atypical painless herpes zoster in a young immunocompetent patient. He was initiated on intravenous acyclovir and made a full recovery after 2 weeks of treatment.

Background In recent years, numerous dosing studies have been conducted to optimize therapeutic antibiotic exposures in patients with serious infections. These studies have led to the inclusion of dose optimization recommendations in international clinical practice guidelines. The last international survey describing dosing, administration and monitoring of commonly prescribed antibiotics for critically ill patients was published in 2015 (ADMIN-ICU 2015). This study aimed to describe the evolution of practice since this time. Methods A cross-sectional international survey distributed through professional societies and networks was used to obtain information on practices used in the dosing, administration and monitoring of vancomycin, piperacillin/tazobactam, meropenem and aminoglycosides. Results A total of 538 respondents (71% physicians and 29% pharmacists) from 409 hospitals in 45 countries completed the survey. Vancomycin was mostly administered as an intermittent infusion, and loading doses were used by 74% of respondents with 25 mg/kg and 20 mg/kg the most favoured doses for intermittent and continuous infusions, respectively. Piperacillin/tazobactam and meropenem were most frequently administered as an extended infusion (42% and 51%, respectively). Therapeutic drug monitoring was undertaken by 90%, 82%, 43%, and 39% of respondents for vancomycin, aminoglycosides, piperacillin/tazobactam, and meropenem, respectively, and was more frequently performed in high-income countries. Respondents rarely used dosing software to guide therapy in clinical practice and was most frequently used with vancomycin (11%). Conclusions We observed numerous changes in practice since the ADMIN-ICU 2015 survey was conducted. Beta-lactams are more commonly administered as extended infusions, and therapeutic drug monitoring use has increased, which align with emerging evidence.